A review on role of metformin as a potential drug for epilepsy treatment and modulation of epileptogenesis

Background: Available anti-seizure medications (ASMs) target the symptomatology of the disease rather than any significant disease/epileptogenesis modifying actions. There are critical concerns of drug resistance and seizure recurrence during epilepsy management. So, drug repurposing is evolving as a paradigm change in the quest for novel epilepsy treatment strategies. Metformin, a well-known anti-diabetic drug has shown multiple pieces of evidence of its potential antiepileptic action.

Objective: This review elucidates various mechanisms underlying the beneficial role of metformin in seizure control and modulation of the epileptogenesis process.

Methods: Preclinical and clinical evidence involving metformin's role in epilepsy and special conditions like tuberous sclerosis have been reviewed in this paper. The putative mechanisms of epileptogenesis modulation through the use of metformin are also summarised.

Results: This review found the efficacy of metformin in different seizure models including genetic knockout model, chemical induced, and kindling models. Only one clinical study of metformin in tuberous sclerosis has shown a reduction in seizure frequency and tumor volume compared to placebo. The suggested mechanisms of metformin relevant to epileptogenesis modulation mainly encompass AMPK activation, mTOR inhibition, protection against blood-brain-barrier disruption, inhibition of neuronal apoptosis, and reduction of oxidative stress. In addition to seizure protection, metformin has a potential role in attenuating adverse effects associated with epilepsy and ASMs such as cognition and memory impairment.

Conclusion: Metformin has shown promising utility in epilepsy management and epileptogenesis modulation. The evidence in this review substantiates the need for a robust clinical trial to explore the efficacy and safety of metformin in persons with epilepsy.